Sharpless Dihydroxylation

The Sharpless Dihydroxylation or Bishydroxylation is used in the
enantioselective preparation of 1,2-diols from prochiral olefins. This
procedure is performed with an
osmium catalyst
and a stoichiometric oxidant [e.g. K3Fe(CN)6 or
N-methylmorpholine oxide (NMO)]; it is carried out in a buffered
solution to ensure a stable pH, since the reaction proceeds more rapidly
under slightly basic conditions. Enantioselectivity is achieved through
the addition of enantiomerically-enriched chiral ligands [(DHQD)2PHAL,
(DHQ)2PHAL or their derivatives]. These reagents are also
available as stable, prepackaged mixtures (AD-mix α and AD-mix β, AD =
asymmetric dihydroxylation) for either enantiopreference.

Mechanism of the Sharpless Dihydroxylation

The ligand accelerates the reaction and transfers the chiral information.

After the dihydroxylated product is released from the complex through
hydrolysis, reoxidation of the metal takes place - sodium chlorite is used in
this example, which can regenerate two equivalents of the catalyst.

M. H. Junttila, O. E. O. Hormi, J. Org. Chem., 2004,
69, 4816-4820.

If the olefin concentration is too high, a second equivalent of the substrate
might bind to the catalytic center in the absence of the chiral ligand, and
undergo a dihydroxylation. This side reaction will decrease the
enantioselectivity.

There has been some speculation regarding the actual addition step, for which
experimental data suggest the possible involvement of two separate steps. Thus,
the question arises during these discussions of whether the key step takes place
via an initial [3+2]-addition, or by a [2+2]-addition followed by expansion of
the metallacycle.

Quantum chemical calculations have shown an initial [3+2]-addition of the OsO4
to be energetically more favorable. However, this energy difference is
substantially smaller in the related Re(VII) oxide additions, for example. (D.
V. Deubel, G. Frenking,
Acc. Chem. Res., 2003, 36, 645.
DOI).